ABSTRACT
The first enantioselective aza-Friedel-Crafts reaction between pyrroles and enamides has been achieved by using a novel H8-BINOL-type imidodiphosphoric acid catalyst. This methodology was also applied to the highly enantioselective aza-Friedel-Crafts reaction between pyrroles and imines. The catalyst loadings in these two reactions are low (0.3-2 mol%). Both processes are amenable to gram scales.
Subject(s)
Amides/chemistry , Amines/chemical synthesis , Diphosphonates/chemistry , Imines/chemistry , Naphthols/chemistry , Pyrroles/chemistry , Amines/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
The first enantioselective synthesis of 5,6-dihydroindolo[1,2-a]quinoxalines is achieved by using a newly developed H8-BINOL-type imidodiphosphoric acid catalyst with low catalyst loading through efficient Pictet-Spengler-type reactions of indolyl anilines with ketones. This methodology also generates phenyl-4,5-dihydropyrrolo[1,2-a]quinoxalines with high yields and excellent enantioselectivities. Moreover, this method was utilized to synthesize an HIV-1 inhibitor with high yield and good enantioselectivity through a one-step procedure.
Subject(s)
Anti-HIV Agents/chemical synthesis , Diphosphonates/chemistry , HIV-1/drug effects , Naphthols/chemistry , Pyrroles/chemical synthesis , Quinoxalines/chemical synthesis , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Catalysis , Ketones/chemistry , Molecular Structure , Pyrroles/chemistry , Pyrroles/pharmacology , Quinoxalines/chemistry , Quinoxalines/pharmacology , StereoisomerismABSTRACT
The first enantioselective synthesis of pyrrolyl-substituted triarylmethanes has been accomplished using a novel imidodiphosphoric acid catalyst, which is derived from two (R)-BINOL frameworks with different 3,3'-substituents. This strategy was also expanded to the synthesis of bis(indolyl)-substituted triarylmethanes with high enantioselectivities, which could only be obtained with moderate ee values in previous reports. These two efficient Friedel-Crafts alkylation processes feature low catalyst loading, broad functional group compatibilities, and the potential to provide practical pathways for the synthesis of enantioenriched bioactive triarylmethanes.
